As a therapy for a disease with a nucleic acid pharmaceutical, there is a method with an antisense oligonucleotide, siRNA, ribozyme, antigene, aptamer, decoy nucleic acid or the like.
An antisense oligonucleotide is an oligonucleotide complementary to mRNA, mRNA precursor or ncRNA (non-coding RNA), such as ribosomal RNA, transfer RNA, miRNA and the like, of the target gene, and a single strand DNA, RNA and/or structural analog thereof which consists of about 8 to 30 bases. The antisense oligonucleotide suppresses the function of mRNA, mRNA precursor or ncRNA by forming a double strand with the target mRNA, mRNA precursor or ncRNA.
A siRNA is a low molecular weight double-strand RNA complementary to the target gene which consists of about 19 to 25 base pairs. It relates to a phenomenon called RNA interference, and suppresses the gene expression by base sequence-specific mRNA degradation.
A ribozyme is RNA with enzyme activity of cleaving a nucleic acid. It cleaves specifically the mRNA of the target gene by forming double strands with the mRNA.
An antigene is an oligonucleotide corresponding to a double strand DNA moiety of the target gene. It suppresses transcription from the DNA to mRNA by forming triple strands with the DNA moiety and oligonucleotide.
An aptamer is a DNA, RNA and/or structural analog thereof which specifically bonds to a specific molecule. It inhibits the function of the target protein by binding to the protein.
A decoy nucleic acid is a short DNA comprising the same sequence with a binding site for a specific transcription modulating factor. It inhibits binding with the transcription modulating factor and gene, and suppresses expression of the gene groups activated by the transcription modulating factor.
Various nucleosides or nucleotides are developed as materials for synthesizing the above nucleic acid pharmaceuticals. Examples include S-oligo (phosphorothioate) which is modified the phosphate moiety of a nucleotide, 2′,4′-BNA (bridged nucleic acid)/LNA (locked nucleic acid) which is modified the sugar moiety of a nucleoside or nucleotide (Patent Documents 1 to 5 and Non-patent Documents 1 to 6) and the like.